{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:39:53Z","timestamp":1784133593714,"version":"3.55.0"},"reference-count":20,"publisher":"IMR Press","issue":"2","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Schol Ed)"],"abstract":"<jats:p>Background: A prior direct clinical and morphological comparison between non-coronavirus disease (COVID) myocarditis diagnosed before the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic and post-COVID myocarditis has not been performed. Purpose: To compare morphological activity, Toll-like receptor distribution, and response to immunosuppressive therapy in patients with non-COVID and post-COVID myocarditis. Methods: In total, 77 patients (52 male and 25 female, 48.7 \u00b1 11.7 years old) with biopsy-proven myocarditis, New York Heart Association (NYHA) class 2 or higher heart failure diagnoses, and an ejection fraction (EF) &lt;45% were included. The exclusion criteria comprised a history of myocardial infarction, verified cardiomyopathies, systemic autoimmune diseases, and viral DNA in the myocardium, except parvovirus B19. A right ventricular endomyocardial biopsy was performed using hematoxylin and eosin and Van Gieson staining assays, alongside the polymerase chain reaction (PCR) for viruses (herpes viruses, parvovirus B19, adeno-, enteroviruses, and SARS-CoV-2). Moreover, immunohistochemical assays were conducted for CD3, CD45, CD68, CD20, nucleocapsid\/spike proteins of SARS-CoV-2, and the subcellular distribution of Toll-like receptors (TLRs) type 4 and 9 (in 38 patients). The steroids (methylprednisolone 24\u201340 mg per day), azathioprine, and mycophenolate mofetil were prescribed. This study was observational and non-interventional. The mean follow-up was 15.0 [6.0; 35.5] months. Results: Myocarditis was diagnosed in 45 patients before the SARS-CoV-2 pandemic (giant cell in one case and lymphocytic in the others). Another 32 patients had post-COVID myocarditis that was positive for RNA or\/and proteins of SARS-CoV-2 (giant cell in one case, eosinophilic in three cases, and lymphocytic in the others). There were no differences in age, NYHA classification, C-reactive protein (CRP) and anti-heart antibodies levels, echocardiographic parameters (mean EF: 30.2 \u00b1 7.8 vs. 28.7 \u00b1 6.7%), parvovirus B19 positivity (22 vs. 34%), methylprednisolone dosages (24\u201340 mg\/day), and death\/transplantation rate (11.1 vs. 9.4%). Differences between non-COVID and post-COVID myocarditis focused on higher CD3, CD 45*, and toll-like receptors (TLR)-4 (4+ vs. 6+) and TLR-9 (0 vs. 2+) levels, alongside subcellular distribution and a better response to therapy ((10% or more increase in EF in 53 vs. 86%* of patients, mean EF (43.9 \u00b1 12.3 vs. 49.8 \u00b1 7.6%*) by the end of follow-up); *p &lt; 0.05). Conclusion: Post-COVID myocarditis is characterized by different morphological types, higher morphological activity, the tendency to increase TLR expression, and an improved response to immunosuppressive therapy compared to non-COVID myocarditis.<\/jats:p>","DOI":"10.31083\/fbs28262","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T05:31:53Z","timestamp":1751434313000},"source":"Crossref","is-referenced-by-count":4,"title":["Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy"],"prefix":"10.31083","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-793X","authenticated-orcid":true,"given":"Olga V.","family":"Blagova","sequence":"first","affiliation":[{"name":"Department of Faculty Therapy \u21161, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-1615","authenticated-orcid":true,"given":"Evgenia A.","family":"Kogan","sequence":"first","affiliation":[{"name":"Department of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3753-9328","authenticated-orcid":true,"given":"Vladimir M.","family":"Novosadov","sequence":"first","affiliation":[{"name":"Department of Faculty Therapy \u21161, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-7207","authenticated-orcid":true,"given":"Valeriy A.","family":"Bryukhanov","sequence":"first","affiliation":[{"name":"Department of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1766-9690","authenticated-orcid":true,"given":"Nikolay V.","family":"Zharkov","sequence":"first","affiliation":[{"name":"Department of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Wenzel P, Kopp S, G\u00f6bel S, Jansen T, Geyer M, Hahn F, et al. Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab. Cardiovascular Research. 2020; 116: 1661\u20131663.","DOI":"10.1093\/cvr\/cvaa160."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Lled\u00f3 GM, Sellares J, Brotons C, Sans M, Ant\u00f3n JD, Blanco J, et al. Post-acute COVID-19 syndrome: a new tsunami requiring a universal case definition. Clinical Microbiology and Infection: the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2022; 28: 315\u2013318.","DOI":"10.1016\/j.cmi.2021.11.015."},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Van Linthout S, Klingel K, Tsch\u00f6pe C. SARS-CoV-2-related myocarditis-like syndromes Shakespeare\u2019s question: what\u2019s in a name? European Journal of Heart Failure. 2020; 22: 922\u2013925.","DOI":"10.1002\/ejhf.1899."},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Gy\u00f6ngy\u00f6si M, Alcaide P, Asselbergs FW, Brundel BJJM, Camici GG, Martins PDC, et al. Long COVID and the cardiovascular system-elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases. Cardiovascular Research. 2023; 119: 336\u2013356.","DOI":"10.1093\/cvr\/cvac115."},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Bohn\u00e9 M, Bohnen S, Willems S, Klingel K, Kivelitz D, Bahlmann E. Acute Lymphocytic Myocarditis in a Young Male Post-COVID-19. Case Reports in Cardiology. 2023; 2023: 7646962.","DOI":"10.1155\/2023\/7646962."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Pietsch H, Escher F, Aleshcheva G, Baumeier C, Morawietz L, Elsaesser A, et al. Proof of SARS-CoV-2 genomes in endomyocardial biopsy with latency after acute infection. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases. 2021; 102: 70\u201372.","DOI":"10.1016\/j.ijid.2020.10.012."},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Blagova O, Lutokhina Y, Kogan E, Kukleva A, Ainetdinova D, Novosadov V, et al. Chronic biopsy proven post-COVID myoendocarditis with SARS-Cov-2 persistence and high level of antiheart antibodies. Clinical Cardiology. 2022; 45: 952\u2013959.","DOI":"10.1002\/clc.23886."},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Frustaci A, Verardo R, Galea N, Lavalle C, Bagnato G, Scialla R, et al. Hypersensitivity Myocarditis after COVID-19 mRNA Vaccination. Journal of Clinical Medicine. 2022; 11: 1660.","DOI":"10.3390\/jcm11061660."},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Craver R, Huber S, Sandomirsky M, McKenna D, Schieffelin J, Finger L. Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c). Fetal and Pediatric Pathology. 2020; 39: 263\u2013268.","DOI":"10.1080\/15513815.2020.1761491."},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Fox SE, Falgout L, Vander Heide RS. COVID-19 myocarditis: quantitative analysis of the inflammatory infiltrate and a proposed mechanism. Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology. 2021; 54: 107361.","DOI":"10.1016\/j.carpath.2021.107361."},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Martinez FO, Combes TW, Orsenigo F, Gordon S. Monocyte activation in systemic Covid-19 infection: Assay and rationale. EBioMedicine. 2020; 59: 102964.","DOI":"10.1016\/j.ebiom.2020.102964."},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Makarov I, Mayrina S, Makarova T, Karonova T, Starshinova A, Kudlay D, et al. Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies. Diagnostics (Basel, Switzerland). 2023; 13: 2212.","DOI":"10.3390\/diagnostics13132212."},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Kinoshita H, Kurashige T, Fukuda T, Morita M, Maeda S, Kanegawa M, et al. The impact that myocarditis for post-acute COVID-19 syndrome may be dermatomyositis-like myocarditis: A case report. Heliyon. 2023; 9: e16512.","DOI":"10.1016\/j.heliyon.2023.e16512."},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Satoh M, Nakamura M, Akatsu T, Iwasaka J, Shimoda Y, Segawa I, et al. Expression of Toll-like receptor 4 is associated with enteroviral replication in human myocarditis. Clinical Science (London, England: 1979). 2003; 104: 577\u2013584.","DOI":"10.1042\/CS20020263."},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Zhao Z, Cai TZ, Lu Y, Liu WJ, Cheng ML, Ji YQ. Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression. Biochemistry. Biokhimiia. 2015; 80: 455\u2013462.","DOI":"10.1134\/S0006297915040094."},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Chimenti C, Verardo R, Scopelliti F, Grande C, Petrosillo N, Piselli P, et al. Myocardial expression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus-negative chronic inflammatory cardiomyopathy. European Journal of Heart Failure. 2017; 19: 915\u2013925.","DOI":"10.1002\/ejhf.796."},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Frustaci A, Galea N, Dominici L, Verardo R, Alfarano M, Scialla R, et al. Interleukin-17A-Correlated Myocarditis in Patients with Psoriasis: Cardiac Recovery following Secukinumab Administration. Journal of Clinical Medicine. 2023; 12: 4010.","DOI":"10.3390\/jcm12124010."},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Frustaci A, Alfarano M, Verardo R, Agrati C, Casetti R, Miraldi F, et al. Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome. European Heart Journal. 2021; 42: 1609\u20131617.","DOI":"10.1093\/eurheartj\/ehaa973."},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Tsch\u00f6pe C, Elsanhoury A, Schlieker S, Van Linthout S, K\u00fchl U. Immunosuppression in inflammatory cardiomyopathy and parvovirus B19 persistence. European Journal of Heart Failure. 2019; 21: 1468\u20131469.","DOI":"10.1002\/ejhf.1560."},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Hudowenz O, Klemm P, Lange U, Rolf A, Schultheiss HP, Hamm C, et al. Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020. European Heart Journal. Case Reports. 2020; 4: 1\u20136.","DOI":"10.1093\/ehjcr\/ytaa286."}],"container-title":["Frontiers in Bioscience-Scholar"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBS\/17\/2\/10.31083\/FBS28262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T05:31:55Z","timestamp":1751434315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBS\/17\/2\/10.31083\/FBS28262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025]]}},"alternative-id":["S1945-0516(25)00128-5"],"URL":"https:\/\/doi.org\/10.31083\/fbs28262","relation":{},"ISSN":["1945-0516","1945-0524"],"issn-type":[{"value":"1945-0516","type":"print"},{"value":"1945-0524","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]},"article-number":"28262"}}